An assay of increased capillary permeability in experimental diabetes is proposed which involves the ultrastructural localization of electron dense markers. Diabetes will be induced in rats chiefly by means of an intra peritoneal injection of alloxan. Previous studies of similar diabetic animals have revealed increased penetration of horseradish peroxidase in the area postrema and skeletal muscle, and more rapid equilibration of I125 PVP between blood and tissue. This study is intended to characterize this vascular leak more completely. (1) We hope to determine its magnitude by substituting larger markers for horseradish peroxidase. (2) The location of the increased permeability will be assayed by using capillaries with differing endothelial structure in various tissues. (3) The specificity of this change for diabetes will be evaluated by comparing alloxan induced diabetes with that due to streptozotocin.